Aug 2026· Molecular Psychiatry· 0 citations· 55 references
Medicine
TL;DR
The observed association between [¹¹C]UCB-J SUVR and RRB severity serves as a hypothesis-generating indicator of synaptic involvement of the behavioral rigidity in ASD, and highlights the complexity of ASD-related synaptic pathology.
PURPOSE
Dopaminergic signalling and glucose metabolism have been implicated in autism spectrum disorder (ASD), yet in vivo evidence in the human brain remains largely unexplored. This study examined subcortical dopamine D2 receptor availability and glucose metabolism in ASD to assess their clinical relevance.
METHODS
In this dual-tracer PET/MR case-control study, 30 autistic and 30 neurotypical adults (age-, sex-, body mass index-, and IQ-matched) underwent [11C]raclopride PET to assess dopamine D2 receptor availability, [1⁸F]FDG PET to measure glucose metabolism and resting-state fMRI to evaluate functional connectivity.
RESULTS
Autistic individuals demonstrated increased D2 receptor availability in the thalamus, with additional increases in the nucleus accumbens and putamen among autistic males compared to neurotypical males. Glucose metabolism was elevated in the thalamus and globus pallidus in ASD relative to NT, and this pattern persisted within both autistic males and autistic females in sex‑stratified comparisons. Globus pallidus and thalamic glucose metabolism correlated positively with social and communication difficulties. Resting-state fMRI analyses revealed diagnosis- and sex-dependent correlations between thalamic D2 receptor availability and functional connectivity.
CONCLUSIONS
This study provides in vivo evidence of elevated subcortical D2R availability and glucose metabolism in autistic adults, a pattern observed across sexes. We also show that D2R availability is tightly linked to glucose metabolism and that D2R-functional connectivity coupling is altered in ASD, both relative to neurotypical adults and between autistic males and females. These findings highlight dopaminergic mechanisms as potential biomarkers and therapeutic targets in ASD.
L. V. Knudsen, M. Vafaee, Z. A. Farahani et al.· European Journal of Nuclear...· 0 citations
An exploratory association between right precuneus GMV and ADOS social-domain scores suggests a possible link between localized structural variation and social symptom severity, although this finding requires replication in longitudinal and clinically richer datasets given their sensitivity to the harmonization strategy.
Gang Xiao, Xiaoshi Li, Yue Qin et al.· Frontiers in Neuroscience· 0 citations
Schizophrenia spectrum disorders (SSDs) are clinically and biologically heterogeneous and lack reliable biomarkers for stratification, treatment response and course prediction. Evidence from postmortem, fluid biomarker, and neuroimaging studies suggests that changes in the blood-brain barrier (BBB) may contribute to pathophysiology in a biologically defined subgroup. However, findings in this context are inconsistent and often based on cross-sectional or indirect measures. This study is a longitudinal, multimodal investigation designed to quantify BBB permeability across disease phases using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and to integrate these measures with deep clinical phenotyping. We recruit inpatients with SSDs and healthy controls (HC). Participants undergo multimodal MRI including DCE-MRI at three time points: acute psychosis (baseline; V1), early treatment (4-6 weeks; V2), and long-term follow-up (2.5 years; V3). Clinical characterization includes standardized measures of psychopathology, functioning and cognition. Blood samples are collected at each visit, while CSF is obtained at V1. DCE-MRI-derived voxel-wise permeability metrics are then analyzed. Primary objectives are to compare BBB leakage cross-sectionally between SSD and HC. Secondary objectives include (i) characterizing spatial and temporal leakage profiles across illness phases, (ii) analyzing associations with psychopathology and biological (e.g., inflammatory) signatures, as well as exploratory identification of subgroups. By providing a longitudinal, BBB-specific neuroimaging framework embedded in a deep phenotyping infrastructure, the IMPACT study aims to elucidate BBB alterations in SSDs and to support stratification approaches in precision psychiatry.
A. Wendl, Amelie Zöllinger, Daniel Lukas et al.· European Archives of Psychia...· 0 citations
Sex differences in brain disorders span age at onset, symptom profiles, disease course and treatment response, and may partly reflect underlying differences in cellular metabolism. Indeed, in vivo evidence of sex-related neurometabolic variation remains sparse, with heterogenous and conflicting findings. Using fast high-resolution whole-brain three-dimensional magnetic resonance spectroscopic imaging, we mapped five brain metabolites in three independent cohorts of healthy participants (total n = 114). In a discovery sample of adolescents scanned at 3 Tesla (3T) (n = 61), males showed higher total N-acetylaspartate (tNAA) across widespread gray matter regions. Regional analyses further revealed opposing sex patterns with a complementary higher total creatine (tCr) observed in females, motivating examination of their ratio as an integrative metabolic index. The tNAA/tCr ratio was consistently higher in males in the discovery sample and this finding was replicated across two independent young-adult samples (3T, n = 26; 7T, n = 27), with a widespread gray and white matter distribution. This tNAA/tCr ratio may link neuronal mitochondrial metabolism with cellular energy buffering, positioning it as a potential index of bioenergetic balance relevant for conditions showing both sex differences and altered neurometabolism, notably multiple sclerosis, Alzheimer disease, and psychosis. Together, these findings reveal a reproducible, distributed metabolic sexual dimorphism in the human brain, and underscore the importance of accounting for sex-specific neurometabolic profiles in studies of brain health and disease.
Edgar Céléreau, F. Lucchetti, P. Steullet et al.· bioRxiv· 0 citations
Major depressive disorder (MDD) is characterized by dysfunction in higher-order cortical regions involved in emotional and cognitive processes; however, its neurobiological basis remains unclear. Pharmacological treatments, including esketamine and sertraline, produce rapid antidepressant effects. We investigated the local intrinsic neural dynamics underlying these antidepressant effects using intrinsic neural timescales (INT), which measure the duration and capacity of information integration in localized brain regions.
A total of 57 healthy controls and 41 patients with MDD were included. All patients with MDD received six intravenous infusions of esketamine (0.25 mg/kg) and two weeks of sertraline treatment. All participants underwent resting-state fMRI to quantify INT alterations at the voxel and brain network levels, followed by spatial correlation analyses linking autocorrelation metrics of INT signals to transcriptomic data from the Allen Human Brain Atlas and PET-derived neurotransmitter receptor maps. The spatial correlation between PLS2 scores and case–control t-statistic maps did not pass rigorous spin permutation testing (
r
= 0.484,
p
= 0.068) and did not meet the conventional significance threshold of 0.05. Accordingly, all subsequent enrichment analyses based on PLS2 results are presented as exploratory preliminary observations for hypothesis generation.
Compared with healthy controls, patients with MDD exhibited significantly elevated INT levels in the left and right precuneus. Following treatment, patients with MDD showed significantly increased INT in the left occipital midline region and left calcarine cortex. At the brain network level, INT levels were significantly reduced in the default mode network (DMN) in patients with MDD compared with healthy controls. Compared with the pre-treatment state, the cerebellar network (CN) showed significantly elevated INT levels after treatment. Partial least squares regression analysis suggested potential associations between INT alterations and spatial gene expression gradients particularly those associated with immune responses, hormonal regulation, neutrophils, regulatory T cells, and glutamatergic synapses. Cell-type enrichment analysis identified excitatory and inhibitory neurons as key cellular contributors. Alterations in INT also correlated with cortical 5-HT1b and NAT receptor density, suggesting a role for inhibitory neurotransmission in temporal integration deficits.
This study advances understanding of treatment-related brain abnormalities in patients with MDD from the perspective of local neural dynamics. These findings support a multiscale pathophysiological framework involving brain connectivity dynamics, molecular architecture, and neurochemical regulation in MDD.
Xiang Liu, Yuanzhi He, Lifeng Li et al.· BMC Psychiatry· 0 citations
INTRODUCTION
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition defined by impairments in social communication and interaction alongside restricted and repetitive patterns of behavior or interests. Alterations in the hippocampus are likely associated with cognitive and behavioral manifestations of ASD. This study aims to map the methods used in Magnetic Resonance Imaging (MRI) of the hippocampus in ASD and to investigate its reported alterations.
METHODS
We performed a literature search using Medical Subject Headings (MeSH) and keywords across PubMed, Embase, BVS, Web of Science, Scopus, Cochrane Library, and PsycINFO. Original case-control, cross-sectional, and longitudinal studies evaluating patients with ASD using MRI were eligible for inclusion. Data was manually extracted and charted in four tables.
RESULTS
A total of 104 studies were included, encompassing neuroimaging modalities such as structural morphometry, diffusion imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, and perfusion imaging. Reported findings across studies included atypical hippocampal overgrowth during early development, reduced N-acetylaspartate levels in children, chronic hypoperfusion extending into early adulthood, hyperrecruitment of specific hippocampal regions that improperly connect with cortical areas, reduced microstructural integrity in adulthood, and a notable decline in hippocampal volume as individuals age.
CONCLUSION
The current evidence suggests that the hippocampus may undergo multimodal alterations in ASD, spanning morphometric, microstructural, metabolic, functional, and perfusion domains, and that these alterations may be age-dependent. Longitudinal research is required to delineate age-specific thresholds for these changes and elucidate their associations with neurodevelopmental outcomes in ASD.
Gabriel Moreli Ribeiro, Érico de Carvalho Leitão Pimentel, Larissa de Goes et al.· Trends in Psychiatry and Psy...· 0 citations